The mechanism of leukocyte activation by chemotactic factors has been studied using electrophysiology fluorescent probe, surface change and ultrastructural techniques. Studies assessing the mechanism of modulating leukocyte locomotion indicate that in neutrophils, secretion of specific granules, which accompanies chemotaxis, is associated with membrane changes and inhibition of chemotaxis. In related experiments it was found that although cAMP inhibited chemotaxis this inhibition correlated with the effect of cAMP on inhibition of cGMP accumulation and not on the locomotory apparatus of the cell per se. Two populations of neutrophils have been identified, purified and functionally distinguished in normal peripheral blood. Clinical studies are currently underway to assess the biological significance of these neutrophil populations. In other clinical studies assessing phagocyte function in patients with compromised host defenses, a patient with markedly increased cGMP and increased microtubule assembly has been identified. The pharmalologic agents levamisole and ascorbate, which effect cGMP and locomotion in vitro, are being studied for their in vivo effects on phagocyte function and the clinical course of selected patients. BIBLIOGRAPHIC REFERENCES: Wyler, D. G. and Gallin, J. I.: Spleen derived chemotactic factor in material infections. A possible mechanism for splenic macrophage accumulation. J. Immunol. 118: 478-484, 1977. Wright, D. G., Bralove, D. A., and Gallin, J. I.: The differential mobilization of human neutrophil granules: Effects of phrobol myristate acetate and ionophore A23187. Am. J. Pathol. 87: 273-284, 1977.